Guanine Nucleotide Regulatory Proteins, G<sub>q</sub> and G<sub>i1/2</sub>, Mediate Platelet‐Activating Factor‐Stimulated Phosphoinositide Metabolism in Immortalized Hippocampal Cells

Shi, Leng‐Chu; Wang, Hoau‐Yan; Horwitz, Joel; Friedman, Eitan

doi:10.1046/j.1471-4159.1996.67041478.x

Cited by 24 publications

(13 citation statements)

References 28 publications

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“…S1PR 2 and S1PR 3 ) might activate cation channels directly in the PMN, as has been suggested in some cell types (42,43). PAF receptors (PAFrs) do indeed activate G q/11 (44), but the inhibition of PAF-mediated calcium entry by DMS (Fig. 13B) suggests that PAFr/G q -dependent calcium entry requires S1P synthesis.…”

Section: S1p-and Store-operated Calcium Entrysupporting

confidence: 51%

Sphingosine 1-Phosphate, a Diffusible Calcium Influx Factor Mediating Store-operated Calcium Entry

Itagaki

Hauser

2003

Journal of Biological Chemistry

108

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Store-operated calcium entry (SOCE) is a fundamental mechanism of calcium signaling. The mechanisms linking store depletion to SOCE remain controversial, hypothetically involving both diffusible messengers and conformational coupling of stores to channels. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid that can signal via cell surface G-protein-coupled receptors, but S1P can also act as a second messenger, mobilizing calcium directly via unknown mechanisms. We show here that S1P opens calcium entry channels in human neutrophils (PMNs) and HL60 cells without prior store depletion, independent of G-proteins and of phospholipase C. S1P-mediated entry has the typical divalent cation permeability profile and inhibitor profile of SOCE in PMNs, is fully inhibited by 1 M Gd 3؉ , and is independent of [Ca 2؉ ] i . Depletion of PMN calcium stores by thapsigargin induces S1P synthesis. Inhibition of S1P synthesis by dimethylsphingosine blocks thapsigargin-, ionomycin-, and platelet-activating factor-mediated SOCE despite normal store depletion. We propose that S1P is a "calcium influx factor," linking calcium store depletion to downstream SOCE.Store-operated calcium entry (SOCE) 1 is the primary mechanism of regulated calcium entry into "non-excitable" cells like immunocytes. The mechanisms governing SOCE are controversial but have centered on two main hypotheses (1). In one model, emptying of endoplasmic reticulum (ER) calcium stores leads to the release of small diffusible messenger molecules that act on channels to increase Ca 2ϩ entry (2). Randriamampita and Tsien (3) found strong suggestions of such a messenger molecule in extracts from Jurkat T-cells. They termed this molecule "calcium influx factor" (CIF).Other hypotheses suggest that store depletion leads to calcium channel activation via direct physical interactions between cell membranes and intracellular structures. The "exocytosis model" (4, 5) of physical interactions suggests that vesicles bearing calcium channels fuse with the cell membrane after store depletion. The "conformational coupling" model suggests that ER calcium store depletion can lead to direct physical interactions between ER proteins such as the IP 3 receptor and cell membrane calcium channels such as TRPC3 (6, 7). No specific molecular mechanisms have been proposed however, that might initiate such physical interactions. Moreover, data has continued to accumulate supporting the existence of an unidentified, low molecular weight CIF (8, 9).Sphingosine 1-phosphate (S1P) is a universally bioactive, small (M r 380) sphingolipid metabolite. S1P is derived from the metabolism of sphingolipids and, most notably, from the actions of sphingosine kinase (10, 11) on sphingosine. In 1991, Zhang et al. (12) showed that S1P induces proliferation in Swiss 3T3 fibroblasts. Since that time, the actions of S1P have been studied in detail, and it has been found to be an important extracellular messenger molecule affecting cell growth, differentiation, adhesion, motility, and survival in many organ...

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Section: S1p-and Store-operated Calcium Entrysupporting

confidence: 51%

Sphingosine 1-Phosphate, a Diffusible Calcium Influx Factor Mediating Store-operated Calcium Entry

Itagaki

Hauser

2003

Journal of Biological Chemistry

108

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“…Various calcium pumps and channels have been identified on the nuclear envelope, including IP 3 , IP 4 , ryanodine receptors, and Ca 2ϩ -ATPase pump (16,40). C-PAF caused a dose-dependent increase in peak calcium transients in isolated nuclei of PCECs (Fig.…”

Section: Signal Transduction Of Paf Receptors In Nucleimentioning

confidence: 99%

Proinflammatory Gene Induction by Platelet-Activating Factor Mediated Via Its Cognate Nuclear Receptor

Marrache

Gobeil

Bernier

et al. 2002

The Journal of Immunology

115

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It has been postulated that intracellular binding sites for platelet-activating factor (PAF) contribute to proinflammatory responses to PAF. Isolated nuclei from porcine cerebral microvascular endothelial cells (PCECs) produced PAF-molecular species in response to H2O2. Using FACS analysis, we demonstrated the expression of PAF receptors on cell and nuclear surfaces of PCECs. Confocal microscopy studies performed on PCECs, Chinese hamster ovary cells stably overexpressing PAF receptors, and isolated nuclei from PCECs also showed a robust nuclear distribution of PAF receptors. Presence of PAF receptors at the cell nucleus was further revealed in brain endothelial cells by radioligand binding experiments, immunoblotting, and in situ in brain by immunoelectron microscopy. Stimulation of nuclei with methylcarbamate-PAF evoked a decrease in cAMP production and a pertussis toxin-sensitive rise in nuclear calcium, unlike observations in plasma membrane, which exhibited a pertussis toxin-insensitive elevation in inositol phosphates. Moreover, on isolated nuclei methylcarbamate-PAF evoked the expression of proinflammatory genes inducible nitric oxide synthase and cyclooxygenase-2 (COX-2) and was associated with augmented extracellular signal-regulated kinase 1/2 phosphorylation and NF-κB binding to the DNA consensus sequence. COX-2 expression was prevented by mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 and NF-κB inhibitors. This study describes for the first time the nucleus as a putative organelle capable of generating PAF and expresses its receptor, which upon stimulation induces the expression of the proinflammatory gene COX-2.

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“…For example, the prostaglandin E 2 receptor EP3D couples to G s and G o (12), platelet-activating factor receptor activates G i and G q (13,14), and the sphingosine 1-phosphate receptors S1P 1 and S1P 2 activate G i and G 12/13 (15). Previous reports suggest that in mediating different cellular events, BLT1 also utilizes different G-proteins, namely pertussis toxin (PTX)-sensitive G i/o and PTX-resistant G q subfamilies of G-proteins (7, 16).…”

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confidence: 99%

Identification of the Intracellular Region of the Leukotriene B4 Receptor Type 1 That Is Specifically Involved in Gi Activation

Kuniyeda

Okuno

Terawaki

et al. 2007

Journal of Biological Chemistry

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. The i3-1 mutant, with a mutation at the i3 amino terminus, exhibited greatly reduced GTP␥S binding but intact inositol phosphate accumulation triggered by leukotriene B 4 stimulation. These results suggest that the i3-1 region is required only for G i activation. Moreover, in the i3-1 mutant, the deficiency in G i activation was accompanied by a loss of the high affinity leukotriene B 4 binding state seen with the wild type receptor. A three-dimensional model of BLT1 constructed based on the structure of bovine rhodopsin suggests that the i3-1 region may consist of the cytoplasmic end of the transmembrane helix V, which protrudes the helix into the cytoplasm. From mutational studies and three-dimensional modeling, we propose that the extended cytoplasmic helix connected to the transmembrane helix V of BLT1 might be a key region for selective activation of G i proteins.Leukotriene B 4 (LTB 4 ) 3 is an inflammatory lipid mediator biosynthesized from membrane phospholipids by sequential enzymatic reactions (1-4). LTB 4 recruits and activates leukocytes, such as granulocytes, macrophages, monocytes, and T-cells, and plays pivotal roles in host defense and the pathogenesis of inflammatory and immune diseases (5, 6). These actions are mediated by two types of G-protein-coupled receptors (GPCRs). One is the LTB 4 receptor type-1 (BLT1), a high affinity LTB 4 receptor highly expressed in leukocytes (7). The other, BLT2, is a low affinity LTB 4 receptor expressed more ubiquitously than BLT1 in human tissues (8 -11).Many GPCRs can activate more than one G-protein subfamily member. For example, the prostaglandin E 2 receptor EP3D couples to G s and G o (12), platelet-activating factor receptor activates G i and G q (13,14), and the sphingosine 1-phosphate receptors S1P 1 and S1P 2 activate G i and G 12/13 (15). Previous reports suggest that in mediating different cellular events, BLT1 also utilizes different G-proteins, namely pertussis toxin (PTX)-sensitive G i/o and PTX-resistant G q subfamilies of G-proteins (7, 16). Promiscuous G-protein coupling enables GPCRs to mediate diverse signals.The molecular determinants of many receptors participating in G-protein coupling and activation have been investigated. With some exceptions, most of these studies emphasize the role of membrane-proximal regions of the second and third intracellular loops and of the cytoplasmic tail of the receptor (17). However, no consensus sequences for G-protein coupling have been clearly identified.We and others have reported that truncation of its cytoplasmic tail does not impair the ability of BLT1 to activate G-proteins (18,19). To identify regions of BLT1 responsible for G-protein coupling, we performed an extensive mutagenesis study of its intracellular domains. Here, we show that BLT1 distinguishes G i from G 16 at the amino terminus of the third intracellular region (the i3-1 region). Furthermore, Scatchard analyses of the i3-1 mutant revealed that BLT1 requires G i coupling to maintain a high affinity state for LTB 4 . A three-dimen-* Thi...

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Guanine Nucleotide Regulatory Proteins, G_q and G_i1/2, Mediate Platelet‐Activating Factor‐Stimulated Phosphoinositide Metabolism in Immortalized Hippocampal Cells

Cited by 24 publications

References 28 publications

Sphingosine 1-Phosphate, a Diffusible Calcium Influx Factor Mediating Store-operated Calcium Entry

Sphingosine 1-Phosphate, a Diffusible Calcium Influx Factor Mediating Store-operated Calcium Entry

Proinflammatory Gene Induction by Platelet-Activating Factor Mediated Via Its Cognate Nuclear Receptor

Identification of the Intracellular Region of the Leukotriene B4 Receptor Type 1 That Is Specifically Involved in Gi Activation

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Guanine Nucleotide Regulatory Proteins, Gq and Gi1/2, Mediate Platelet‐Activating Factor‐Stimulated Phosphoinositide Metabolism in Immortalized Hippocampal Cells

Cited by 24 publications

References 28 publications

Sphingosine 1-Phosphate, a Diffusible Calcium Influx Factor Mediating Store-operated Calcium Entry

Sphingosine 1-Phosphate, a Diffusible Calcium Influx Factor Mediating Store-operated Calcium Entry

Proinflammatory Gene Induction by Platelet-Activating Factor Mediated Via Its Cognate Nuclear Receptor

Identification of the Intracellular Region of the Leukotriene B4 Receptor Type 1 That Is Specifically Involved in Gi Activation

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Guanine Nucleotide Regulatory Proteins, G_q and G_i1/2, Mediate Platelet‐Activating Factor‐Stimulated Phosphoinositide Metabolism in Immortalized Hippocampal Cells